Milk production by a mammal is ultimately limited by the amount of mammary parenchyma (secretory tissue) in the mammary gland. Typically, milk yield has been found to be highly correlated with parenchyma wet weight, dry weight, dry fat-free weight and total gland DNA. In 43 Proc. N.Z. Soc. Anim. Prod. 71 (1983), Davis et al attributed increased milk production in genetically superior animals entirely to increased udder volume which is also related to the quantity of parenchyma cells.
Classical evidence indicates that mammary parenchyma growth is directed by pituitary, ovarian, adrenal, placental or locally-derived tissue factors. See Cowie, 15 Mono-graphs on Endocrinology (1980) and U.S. Pat. No. 4,521,409 issued June 4, 1985 to Bauman and Sejrsen, in which it is disclosed that growth of mammary parenchyma in a ruminant can be increased by administering a growth hormone (somatotropin) into the ruminant's blood stream between about the onset of puberty and about the first parturition (preferably about the first conception).
If administered into an animal's blood stream, most mitogens for mammary parenchyma cells bind additionally to receptors in many of the animal's other tissues. Due to such dilution of the desired effect on mammary growth-stimulating receptors, increasing mammary parenchyma via administration into the blood stream would be expected to require relatively large quantities of such mitogens. Hence there is great incentive to develop a practical technique for increasing the milk production capacity and/or efficiency of a mammal that is not dependent on administration into the mammal's blood stream.
Using rabbits, mice and rats that were physiologically abnormal, i.e., ovariectomized and/or pretreated (e.g. with a reproductive hormone) to induce pseudopregnancy, studies have been made of effects on mammary gland development by subcutaneous injection of a somatotropin and/or other hormones, implants that released cholera toxin, or intraductal injection of "lactogenic hormone". Lyons et al, 50 Proc. Soc. Exper. Biol. Med. 308-11 (1942) and 14 Recent Prog. Hormone Res. 219-54 (1958); Fiddler et al, 49 J. Endocrin. 459-69 (1971); Daniel et al, 224 Sci. 1245-47 (1984); and Silberstein et al, 81 Proc. Natl. Acad. Sci. U.S.A. 4950-54 (1984). Based on other studies using rabbits that were pregnant or pretreated (e.g. with a reproductive hormone) to induce pseudo-pregnancy, it has been reported that intraductal injection of prolactin or "lactogenic hormone" induced lactation. Bradley et al, 14 J. Endocrin. 28-36 (1956) and Meites et al, 150 Amer. J. Physiol. 394-99 ( 1947). Others have studied in vitro effects of mitogens such as an epidermal growth factor, with or without insulin, on the growth of cultured mammary cells of various animal species. Imagawa et al, 79 Proc. Natl. Acad. Sci. U.S.A. 4074-77 (1982); Taketani et al, 113(3) Endocrin. 871 (1983) and 80 Proc. Natl. Acad. Sci. U.S.A. 2647-50 (1983); Tonelli et al, 285 Nature 250-52 (1980); and Turkington, 57 Exper. Cell Res. 79-85 (1969). The disclosures cited in this paragraph are incorporated here by reference.